Hydrogen peroxide (H2O2) is a biologically derived stable form of 'active oxygen' which is present in several tissues of the anterior segment of the eye. Although intracameral or intravitreal injections of H2O2 have shown to induce significant morphological changes in tissue of the anterior uvea, no study has addressed the potential pharmacological effect of H2O2 in the anterior segment of the eye. These studies are needed because H2O2 may interfere with neurotransmission in autonomic nerves in the anterior uvea which in turn could affect aqueous humor dynamics. Furthermore, H2O2 may alter the pharmacology of receptors and their signal transduction pathways in the anterior uvea in a manner similar to that reported in the brain and in some peripheral tissues. We hypothesize that oxidative stress induced by H2O2 can modify the output of norepinephrine (NE) from sympathetic nerves in the iris-ciliary body. Effects caused by H2O2 may affect the output of NE by an effect on the release process and/or via an effect on the activity of prejunctional receptors located on sympathetic nerve terminals. The overall objective of the present study is, therefore, to investigate the effect of H2O2 on NE release from the rabbit iris-ciliary body. Experiments in the present project have been designed to answer the following questions: (i) does H2O2 alter the release and/or availability of NE in the anterior uvea: (ii) are second messengers such as calcium, cGMP, cAMP and prostaglandins involved in the effects caused by H2O2 on sympathetic neurotransmission: (iii) is there a relationship between catalase activity, H2O2 levels and the output of NE and NPY in the aqueous humor and iris-cillary body: (iv) does ocular hypotensive effects of H2O2 involve changes in sympathetic neurotransmission and/or prostaglandin release? In summary, we will examine the effect of H2O2 on basal and evoked norepinephrine release in the rabbit iris-ciliary body both in vitro and in vivo. The results of this study will improve our understanding of the effect of H2O2 on neurotransmission and will advance our knowledge of the mechanism of oxidative stress induced damage in the anterior uvea. Furthermore, we hope that these studies may reveal a new role for H2O2 in ocular physiology and/or pharmacology. We anticipate that the findings of this project will be applicable to diseases of the anterior segment of the eye such as glaucoma, uveitis or cataracts.